title: Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position.
abstract: We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution. We discovered classes of DNA-binding factors that strictly avoided, could tolerate or tended to overlap with nucleosomes. Using ATAC-seq maps of human CD4(+) T cells from a proband obtained on consecutive days, we demonstrated the feasibility of analyzing an individual's epigenome on a timescale compatible with clinical decision-making.
authors.affiliation: 1] Department of Genetics, Stanford University School of Medicine, Stanford, California, USA. [2] Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, USA. [3] Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Buenrostro
authors.forename: Paul G
authors.initials: PG
authors.lastname: Giresi
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Zaba
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenleaf
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002469:Cell Separation; D002843:Chromatin / Q000737:chemistry; D019295:Computational Biology / Q000379:methods; D004268:DNA-Binding Proteins / Q000737:chemistry*; D019281:Dimerization; D004742:Enhancer Elements, Genetic; D057890:Epigenomics; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D009707:Nucleosomes / Q000737:chemistry*; D016133:Polymerase Chain Reaction / Q000379:methods; D014157:Transcription Factors / Q000737:chemistry
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D009707:Nucleosomes; D014157:Transcription Factors